ORIGINAL RESEARCH ARTICLE published: 21 March 2012 doi: 10.3389/fonc.2012.00025 CyberKnife boost for patients with cervical cancer unable to undergo brachytherapy Jonathan Andrew Haas 1*, Matthew R. Witten2, Owen Clancey 2, Karen Episcopia2, Diane Accordino1 and Eva Chalas 3 1 Division of Radiation Oncology, Winthrop-University Hospital, Mineola, NY, USA 2 Division of Medical Physics, Winthrop-University Hospital, Mineola, NY, USA 3 Division of Gynecologic Oncology, Winthrop-University Hospital, Mineola, NY, USA Edited by: Standard radiation therapy for patients undergoing primary chemosensitized radiation for Brian Timothy Collins, Georgetown carcinomas of the cervix usually consists of external beam radiation followed by an intra- Hospital, USA cavitary brachytherapy boost. On occasion, the brachytherapy boost cannot be performed Reviewed by: Sean Collins, Georgetown University due to unfavorable anatomy or because of coexisting medical conditions. We examined the Hospital, USA safety and efficacy of using CyberKnife stereotactic body radiotherapy (SBRT) as a boost Brian Timothy Collins, Georgetown to the cervix after external beam radiation in those patients unable to have brachytherapy Hospital, USA to give a more effective dose to the cervix than with conventional external beam radiation *Correspondence: alone. Six consecutive patients with anatomic or medical conditions precluding a tandem Jonathan Andrew Haas, Division of Radiation Oncology, and ovoid boost were treated with combined external beam radiation and CyberKnife boost Winthrop-University Hospital, 264 Old to the cervix. Five patients received 45 Gy to the pelvis with serial intensity-modulated radi- Country Road, Mineola, NY 11501, ation therapy boost to the uterus and cervix to a dose of 61.2Gy.These five patients received USA. an SBRT boost to the cervix to a dose of 20 Gy in five fractions of 4 Gy each. One patient e-mail: [email protected] was treated to the pelvis to a dose of 45 Gy with an external beam boost to the uterus and cervix to a dose of 50.4 Gy. This patient received an SBRT boost to the cervix to a dose of 19.5 Gy in three fractions of 6.5 Gy. Five percent volumes of the bladder and rectum were kept to ≤75 Gy in all patients (i.e., V75 Gy ≤ 5%). All of the patients remain locally controlled with no evidence of disease following treatment. Grade 1 diarrhea occurred in 4/6 patients during the conventional external beam radiation. There has been no grade 3 or 4 rectal or bladder toxicity. There were no toxicities observed following SBRT boost. At a median follow-up of 14 months, CyberKnife radiosurgical boost is well tolerated and efficacious in providing a boost to patients with cervix cancer who are unable to undergo brachytherapy boost. Further follow-up is required to see if these results remain durable. Keywords: cervix, SBRT, brachytherapy, CyberKnife INTRODUCTION instance, Barraclough et al. delivered a total dose of 54–70 Gy Standard radiation therapy for cervical carcinoma patients under- through the addition of an EBRT boost to patients unable to going primary chemosensitized radiation therapy usually consists receive the brachytherapy boost. The majority of patients devel- of external beam therapy followed by an intracavitary brachyther- oped a central recurrence in less than 5 years and had a 5- apy boost (Eifel et al., 2004). Using this approach, the brachyther- year overall survival rate of 49.3% (Barraclough et al., 2008). apy serves to provide a tumorical dose to the cervix while limiting This compares unfavorably to combined external beam therapy the dose to surrounding anatomy, such as the bladder and rectum, with a brachytherapy boost where 5-year local control and sur- which have a lower dose tolerance. Typically, external beam radia- vival are in the 60–70% range (Rose et al., 1999; Eifel et al., tion delivers a dose of approximately 45 Gy to encompass the pri- 2004). mary tumor and regional pelvic lymph nodes. The brachytherapy Brachytherapy takes advantage of the inverse square law in that boost results in a total dose ranging from 70 to 95 Gy to the pri- high doses of radiation are given to the target (cervix in this case) mary tumor (assuming an alpha/beta ratio of 10 Gy), depending and low doses are given to the normal anatomy by moving them on tumor stage and anatomy. out of the way with packing material exploiting the rapid dose fall- In certain circumstances, the brachytherapy boost may not off and inhomogeneous dose distribution seen with brachyther- be feasible due to coexisting medical conditions, unfavorable apy. Stereotactic body radiotherapy (SBRT) provides a poten- anatomy, or patient refusal to undergo the procedure. In these tial alternative method to boost the cervix in those cases where cases, a higher dose of external beam radiation (EBRT) may brachytherapy is not performed. SBRT emulates brachytherapy be given, but the total dose delivered is usually less than by having multiple non-coplanar beams intersecting at the target when a brachytherapy procedure is performed. Predictably, the (cervix) delivering a high therapeutic dose while minimizing beam results when brachytherapy is not performed are inferior. For traversal through normal anatomy reducing dose to these areas. By www.frontiersin.org March 2012 | Volume 2 | Article 25 | 1 Haas et al. CK boost for cervical cancer prescribing to a specific isodose line (i.e., the dose line that covers dose to the bladder and/or rectum a point dose of up to 75 Gy was the volume of interest), the tumor receives an inhomogeneous allowed. dose similar to that delivered with brachytherapy. Technological Following conventionally fractionated radiation therapy, advances using the CyberKnife (Accuray Incorporated, Sunnyvale, patients had three to four gold fiducial markers placed into the CA, USA), a robotic radiation delivery system, allow more precise cervix and upper vagina. Fiducial placement began with a lidocaine targeting and delivery of radiation to the cervix while sparing nor- gel and a betadine prep and proceeded under direct visualization in mal anatomy compared to conventional radiation. This potentially the lithotomy position. The fiducials were placed into the cervix allows dose escalation to the cervix to a dose comparable to the at the 3 and 9 o’clock position and superiorly into the vaginal brachytherapy boost while respecting the normal tissue tolerance fornices in an orientation to prevent overlap in the plane of the of the bladder and rectum. The CyberKnife’s use of a large number X-ray imaging. Treatment planning CT scans at a slice thickness of small radiation beams also allows delivery of an inhomogeneous of 1.25 mm and an MRI scan using a slice thickness of 1–2 mm dose distribution similar to that of brachytherapy (Fuller et al., were performed 1 week after fiducial placement. All pretreatment 2008). imaging was performed with the patient in the same position used Another important aspect of CyberKnife delivered SBRT to for SBRT delivery. The pulse sequence used for MRI acquisition the cervix is motion tracking. The cervix is not a fixed pelvic was gradient echo which maximized the signal void attributable organ, rather one that is subject to movement during treat- to the fiducials and allowed for clear visualization of the fiducials ment. For example, a study from the University of California at in the MR image. This allowed for the fusion of the MR and CT San Diego showed that the cervix can move as much as 18 mm data sets using the fiducials. The gross tumor volume (GTV) was during intensity-modulated radiation therapy (IMRT) treatment contoured by the attending radiation oncologist using both CT (Haripotepornkul et al., 2011); other studies of cervical motion and MRI images to accurately delineate the cervical anatomy and have shown similar movement (Hombaiah et al., 2006; Taylor and to define the interface between the cervix and anterior wall of the Powell, 2008). Given the large movement possible, continuous rectum. tracking of the cervix during treatment is imperative in ensur- All patients received SBRT boost using the CyberKnife system ing proper delivery of dose to the tumor particularly when giving (Accuray Incorporated, Sunnyvale, CA, USA) which consists of a larger than conventional daily doses of radiation as is the case with 6-MV linear accelerator mounted on a robotic arm. Using this the SBRT. Lastly, since SBRT is given in a week, the total treat- system two orthogonal kilovoltage X-ray imagers provide real- ment time frame is comparable to external beam therapy with a time image guidance and automatic correction for movement of brachytherapy boost thus limiting the deleterious effect observed the cervix throughout the treatment. There were typically 150– in prolonged treatments extending beyond 7 weeks (Fyles et al., 200 non-coplanar beams delivered during each treatment session. 1992; Girinsky et al., 1993; Lanciano et al., 1993; Perez et al., 1995; Target tracking and patient positioning were accomplished by reg- Petereit et al., 1995). istering the location of the fiducial markers in the real-time images In this report, we present preliminary local control results on to their planning CT location. Imaging was performed approxi- the treatment of six patients with cervical cancer who did not mately once per minute. The robotic delivery system automatically have a brachytherapy boost and were treated with an SBRT boost changes the linear accelerator’s position to correct for both rota- resulting in a total dose of 77–85 Gy to the cervix. tional and translational movement of the patient and cervix during treatment. The total clinical accuracy for treatment is less than MATERIALS AND METHODS 1mm(Kilby et al., 2010). Treatments were delivered on three or This is a retrospective chart review of cervical cancer patients five consecutive days. Patients had a bowel prep including Dulco- treated with combined external beam radiation and SBRT boost to lax (Boehringer, Germany) and a fleet enema on the morning of the cervix at Winthrop-University Hospital from 3/2009 to 8/2011.